A study was made of the properties of the two structural models that had previously been constructed for the eukaryotic triple complex eRF1 : mRNA : tRNA^Phe with eRF1 accommodated in the A site and tRNA^Phe, in the P site of the ribosome. The structure of the complex was described using a high-resolution NMR structure of the human eRF1 M domain. The distribution of chemical crosslinks between mRNA and eRF1 was studied for the two models, which made it possible to decide about the positioning of eRF1 in the A site relative to the mRNA stop codon. Molecular dynamics was used to simulate the distribution of close contacts (<7 Å) between the photoactivatable azido group of modified mRNA analogs and eRF1 residues in the complex. Analysis of the structures of 12 analogs containing a modified nucleotide with the photoactivatable group in a position from +4 to +9 showed that only one model of eRF1 binding with mRNA in the A site well agreed with experimental data on chemical crosslinking. A new feature of the model selected is that the C domain of eRF1 is close to the mRNA stop-codon nucleotides, which explained the experimental findings.